A general model for Multilocus Epistatic interactions in case-control studies

Zhong Wang, Tian Liu, Zhenwu Lin, John Hegarty, Walter Koltun, Rongling Wu

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background:Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology:We develop a general model for testing high-order epistatic interactions for a complex disease in a case-control study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions:Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis.

Original languageEnglish (US)
Article numbere11384
JournalPloS one
Volume5
Issue number8
DOIs
StatePublished - Oct 19 2010

Fingerprint

epistasis
case-control studies
Case-Control Studies
Inflammatory Bowel Diseases
Genes
Single Nucleotide Polymorphism
Disease Progression
Alleles
Complex networks
Testing
loci
Population
inflammatory bowel disease
quantitative genetics
Identification (control systems)
Sampling
genes
testing
alleles
sampling

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Wang, Zhong ; Liu, Tian ; Lin, Zhenwu ; Hegarty, John ; Koltun, Walter ; Wu, Rongling. / A general model for Multilocus Epistatic interactions in case-control studies. In: PloS one. 2010 ; Vol. 5, No. 8.
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A general model for Multilocus Epistatic interactions in case-control studies. / Wang, Zhong; Liu, Tian; Lin, Zhenwu; Hegarty, John; Koltun, Walter; Wu, Rongling.

In: PloS one, Vol. 5, No. 8, e11384, 19.10.2010.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A general model for Multilocus Epistatic interactions in case-control studies

AU - Wang, Zhong

AU - Liu, Tian

AU - Lin, Zhenwu

AU - Hegarty, John

AU - Koltun, Walter

AU - Wu, Rongling

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AB - Background:Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology:We develop a general model for testing high-order epistatic interactions for a complex disease in a case-control study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions:Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis.

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